Effect of Maternal Exercise in Women with Obesity on Offspring Mesenchymal Stem Cell Metabolism Grant uri icon

abstract

  • NIH R01 (PI: Broskey) $3,369,300 Jan 2024-Jan 2029
    Effect of Maternal Exercise in Women with Obesity on Offspring Mesenchymal Stem Cell Metabolism
    Role: CoI
  • Obesity in pregnancy increases the risk for excessive adiposity in offspring. Our preliminary data and published studies indicate that exercise initiated during pregnancy in sedentary women with obesity lowers infant BMI z-scores and body fat percentages, especially when resistance exercise is included. However, there are few human mechanistic studies to assess how maternal exercise induces changes to infant cellular metabolism. Infant umbilical cord-derived mesenchymal stem cells (MSCs) are a unique model to explore offspring cellular phenotypes in humans. Our evidence suggests an improved cellular phenotype in infant MSCs from maternal aerobic exercise and even greater with resistance exercise. However, these MSC outcomes were observed in pregnant women without obesity, so it is uncertain if other modes of maternal exercise might improve the MSC phenotype associated with maternal obesity exposure. Our parent RCT is a longitudinal prospective study enrolling 284 pregnant women with obesity at <16 weeks gestation, randomized to aerobic exercise, resistance exercise, or usual care. The objective of this ancillary study is to use the MSC model to determine if maternal exercise mitigates the adverse effects of gestational obesity exposure. The overarching hypothesis is that resistance exercise will manifest improved MSC metabolism as compared to aerobic or control.
  • besity in pregnancy increases the risk for excessive adiposity in offspring, which tracks into adulthood and can perpetuate across generations. Our preliminary data and published studies indicate that exercise initiated during pregnancy in sedentary women with obesity lowers infant BMI z-scores and body fat percentage. These benefits to infant health are more profound with resistance exercise during pregnancy. However, there are few mechanistic studies in humans aimed at discerning mechanisms of maternal exercise-induced changes to infant cellular metabolism. Our findings support the use of infant umbilical cord-derived mesenchymal stem cells (MSCs) as a model to explore offspring cellular phenotypes in humans. Importantly, these MSCs are of the same lineage that derive postnatal tissues and thus, can be differentiated into mesodermal cell types important for regulating whole-body metabolism, such as myocytes and adipocytes. We have evidence of improved cellular phenotype in infant MSCs exposed to maternal aerobic exercise (AE) with the greatest improvements in MSC metabolism from maternal resistance exercise (RE). The objective of the proposed study is to determine if maternal exercise mitigates the adverse consequences of gestational obesity exposure using the MSC model in an ancillary study from a parent grant that is randomizing pregnant women with obesity to AE, RE, or usual care control. A secondary objective is to determine if the MSC metabolic profiles are associated with infant whole-body health outcomes at 1-, 6-, and 12-months of age. We will test this hypothesis in 64 subjects from the parent trial. In Aim 1, we will determine the impact of maternal exercise in women with obesity on infant MSC substrate metabolism and bioenergetic efficiency. These data will be associated with infant whole-body resting energy expenditure and substrate oxidation via indirect calorimetry over the first year of life. In Aim 2, we will determine the role of maternal exercise mode in women with obesity on infant MSC adipogenesis and lipid storage. These data will be associated with infant body composition as measured by DXA over the first year of life. In Aim 3, MSCs will undergo a multiomics approach where we will identify candidate genes and epigenetic signatures of maternal exercise mode. These outcomes will be correlated with blood metabolomic measures in the infant to establish gene-metabolite pathways. Leveraging a large, rigorous RCT in pregnant women with obesity, this will be the first study to identify how maternal exercise affects offspring cellular metabolism. This work will have significant impact by translating infant cellular metabolic data with whole-body metabolic data across the first year of life.

date/time interval

  • September 2023 - December 2025